Ketone bodies are produced in the liver, mainly from the oxidation of fatty acids, and are exported to peripheral tissues for use as an energy source. They are particularly important for the brain, which has no other substantial non-glucose-derived energy source. The two main ketone bodies are 3-hydroxybutyrate and acetoacetate. Biochemically, abnormalities of ketone body metabolism can be subdivided into three categories: ketosis, hypoketotic hypoglycemia, and abnormalities of the 3-hydroxybutyrate/acetoacetate ratio.
An abnormal elevation of the 3-hydroxybutyrate/acetoacetate ratio usually implies a non-oxidized state of the hepatocyte mitochondrial matrix resulting from hypoxia-ischemia or other causes.
The presence of ketosis normally implies that lipid energy metabolism has been activated and that the entire pathway of lipid degradation is intact. In rare cases, ketosis reflects an inability to utilize ketone bodies. Ketosis is normal during fasting, after prolonged exercise, and when a high-fat diet is consumed. During the neonatal period, infancy and pregnancy, times at which lipid energy metabolism is particularly active, ketosis develops readily.
Pathologic causes of ketosis include diabetes, ketotic hypoglycemia of childhood, corticosteroid or growth hormone deficiency, intoxication with alcohol or salicylates, and several inborn errors of metabolism.
The formation of ketone bodies is increased when lipolysis is increased e.g. in insulin deficiency (diabetes mellitus; in particular type I diabetics), when the glucagon concentration is increased and in a fasting state. In such cases the normal physiological concentration of less than 7 mg/dl can increase to more than 10-fold. Over the past years 3-hydroxybutyrate has proven to be an extremely reliable parameter for monitoring an insulin therapy.
The absence of ketosis in a patient with hypoglycemia is abnormal and suggests the diagnosis of either hyperinsulinism or an inborn error of fat energy metabolism.
Accordingly, ketone bodies are an interesting diagnostic target, particularly for diabetes. Therefore, there is an ongoing need for robust and sensitive test-systems for ketone bodies, especially 3-hydroxybutyrate. The ratio of 3-hydroxybutyrate to acetone or acetoacetic acid is normally 3:1. In keto-acidoses the ratio increases to 6:1 to 12:1. A suitable 3-HBDH should enable the development of a quantitative test for 3-hydroxybutyrate.